Our study revealed novel functions of DLL4 in cell stemness and immune infiltration, including NET formation and T cell exclusion, which collectively contributed to THP neoadjuvant therapy resistance in HER2+ BC. Furthermore, we provided a CAR-T-based therapy to sensitize the THP neoadjuvant therapy.

The economic viability of dual HER2-targeted therapy was most pronounced in patients with node-positive high-risk early breast cancer. This study highlights the potential of dual HER2-targeted therapy as a cost-effective addition for these cases.

In this regard, we also found that the savings produced from switching from the traditional intravenous treatment to the subcutaneous one would allow EsSalud to afford full annual costs of 2 additional treatments, but without increasing their budget. This would cover 7% of the gap of 29 patients who do not have access to full treatment.

P2, N=220, Active, not recruiting, West German Study Group | Recruiting --> Active, not recruiting | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Aug 2015 --> Jan 2025

P2, N=402, Recruiting, West German Study Group | Not yet recruiting --> Recruiting

P2, N=86, Completed, UNICANCER | Active, not recruiting --> Completed

No abstract available

Consequently, we determined that the patient presented with a condition similar to immune thrombocytopenic purpura (ITP) and selected a treatment approach consisting of eltrombopag, a thrombopoietin receptor agonist. Although uncommon, anti-HER2 antibodies can cause severe thrombocytopenia. Furthermore, if thrombocytopenia persists after treatment discontinuation and the administration of corticosteroids, exploring treatment options aligned with managing ITP is essential.

In those with RD, 36% lost HER2(+) status; IDFS events appeared similar in those with HER2(+) RD versus those with HER2(-) RD. The BM events seen in those with RD and pCR highlights the need for more effective therapy in NAST and adjuvant setting to minimize BM risk.

Dual human epidermal growth factor receptor 2(HER2)blockade with trastuzumab(H)and pertuzumab(P)combined with docetaxel and carboplatin(TCb)is a standard neoadjuvant therapy for HER2-positive breast cancer patients. 4 cycles of T-DM1+P). Simultaneous administration of H and P enables a reduced administration time, which would benefit both patients and healthcare providers.

Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved an adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

Undifferentiated thyroid cancer (ATC) is highly malignant and does not respond well to sorafenib (SRF) treatment owing to the lack of specificity of SRF targeting...Therefore, we developed a pH-responsive nano-targeted drug delivery systems using human serum albumin (HSA) as a carrier to generate manganese dioxide (MnO2)@HSA nanoparticles (NPs), then encapsulated SRF and the fluorescent dye indocyanine green (ICG) and finally modifyed the targeting antibody pertuzumab in the outer layer of the nano complexes, resulting in SRF/ICG/MnO2@HSA-pertuzumab (HISMP) NPs...In vivo MR/NIRF imaging experiments confirmed that the HISMP NPs specifically aggregated at tumor sites and have good in vivo MR/NIRF imaging ability and effective anti-tumor activity. The nano-delivery system is expected to provide a theoretical foundation for the efficient ATC diagnosis and therapy.

The patient received neoadjuvant chemotherapy with epirubicin and cyclophosphamide, followed by docetaxel, trastuzumab, and pertuzumab...A liver biopsy following treatment with trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-Dxd) revealed HER2-negative status. Cyclin-dependent kinase (CDK) 4/6 inhibitor combination endocrine therapy has been continued for 16 months to date while maintaining tumor shrinkage. It is essential to perform a rebiopsy during treatment to optimize therapy based on the subtype.

P2, N=53, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting

Our results are in line with the CLEOPATRA and EMILIA studies, but long-term responders in the arm A may have impacted our results. The absence of difference in term of PFS in first metastatic line may be explained by a selection bias, as patients in the arm A potentially have more aggressive forms.

HER2-targeted drugs such as HerceptinTM (trastuzumab), PERJETA® (pertuzumab) and KADCYLA® (adotrastuzumab emtansine) are beneficial for HER2-positive breast cancer patients who will inhibit cell signaling pathways. If the FISH results are negative for HER2 IHC equivocal, this is considered HER2-Low. Significantly, Enhertu has shown a promising objective response in HER2-Low breast cancer patients.

P2, N=20, Suspended, University of Rochester | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2026

P3, N=516, Active, not recruiting, Helsinki University Central Hospital | Trial primary completion date: Dec 2021 --> Jul 2025

P2, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2024 --> Nov 2024

Targeted therapies like trastuzumab deruxtecan (T-DXd), trastuzumab, pertuzumab, and T-DM1 have revolutionized HER2-positive metastatic breast cancer (MBC) treatment. Personalized approaches have boosted HER2-positive MBC outcomes, and ongoing research is crucial to uncover new treatments and biomarkers, potentially elevating long-term response rates and prognoses. This may aid in providing new direction to breast cancer clinics.

Managing Li-Fraumeni syndrome (LFS) and its associated cancers, particularly in young patients, necessitates a comprehensive and multidisciplinary approach. Early genetic testing for TP53 mutations is crucial in identifying LFS, enabling personalized treatment plans and proactive surveillance strategies.

In November 2013, for neck nodal progression, seven cycles of chemotherapy (cisplatin and epirubicin) associated with a humanized monoclonal antibody-targeting HER 2 therapy (trastuzumab and pertuzumab) were performed, with a marked response rate. In primary ductal adenocarcinoma of the lacrimal gland, early diagnosis and multimodal treatments could be crucial, considering its often aggressive tendency. Considering the lack of treatment guidelines, case report recording can be useful in patient management.

The TCbHP regimen (docetaxel, carboplatin, trastuzumab, and pertuzumab) as neoadjuvant chemotherapy was given. Our clinical experience suggests that neoadjuvant chemotherapy followed by modified radical mastectomy can be effective for treating such rare cases. The patient achieved pCR, which can provide a therapeutic strategy for effective treatment of similar OBCs.

P1/2, N=39, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2024 --> Jul 2025 | Trial primary completion date: Nov 2024 --> Jul 2025

P4, N=250, Not yet recruiting, Danish Breast Cancer Cooperative Group

HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

The iDFS benefit was seen in the hormone receptor-negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.

P3 | N=808 | CLEOPATRA (NCT00567190) | Sponsor: Genentech, Inc. | "REVEAL GENOMICS S.L...released further evidence supporting HER2DX, the world’s first specialized genomic test for HER2+ breast cancer. These results were obtained in collaboration with F. Hoffmann-La Roche Ltd (Basel, Switzerland) after analyzing HER2DX in tumor samples from the CLEOPATRA phase III clinical trial (NCT00567190)....For the first time, the investigators evaluated the ability of the HER2DX ERBB2 mRNA score to predict long-term survival outcomes in 214 patients treated with THP in the pivotal CLEOPATRA phase III trial3. The results showed a strong association of HER2DX ERBB2 mRNA score with PFS and OS....Detailed results of this study will be presented at an upcoming medical congress and submitted for publication."

The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.

The observed preference for SC administration not only aligns with the imperative of adapting health systems to facilitate broad access to new cancer therapies but also underscores the importance of considering patient experiences and economic implications in shaping treatment strategies. These insights are crucial for healthcare policymakers, clinicians, and stakeholders in optimizing healthcare resources and enhancing the overall quality of BC care.

P4, N=100, Not yet recruiting, Fudan University

SRS affords effective LTC for selected patients with BM from HER-2 positive breast cancer. Concurrent pertuzumab improved LTC and OS but at the same time increased the risk for overall, but not symptomatic, ARE.

A 41-year-old Caucasian female with SDS developed stage IV triple-positive [estrogen positive, progesterone positive, and human epidermal growth factor receptor 2 (HER2) positive] invasive ductal carcinoma of the left breast with liver metastases...Based on her underlying SDS, paclitaxel was favored over docetaxel due to the reduced risk of myelosuppression and weekly dosing schedule. Her regimen included weekly paclitaxel with trastuzumab and pertuzumab every 21 days...G-CSF facilitated ongoing chemotherapy administration and reduced the risk of infection leading to an optimal therapeutic outcome. There should be careful consideration of early G-CSF use in patients with SDS to optimize continuous chemotherapy dosing.

HER2-positive breast cancer exhibits HER2 protein overexpression or gene amplification, benefiting from HER2-targeted therapies like trastuzumab and pertuzumab. Challenges remain in accurately classifying HER2-low tumors and optimizing treatment efficacy, necessitating ongoing research and innovative diagnostic methods. Understanding the heterogeneity and evolving landscape of HER2 status in breast cancer is crucial for advancing personalized treatment strategies and improving patient outcomes.

P=N/A, N=148, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Trial completion date: Sep 2026 --> Jan 2027 | Initiation date: Sep 2023 --> Jan 2024 | Trial primary completion date: Sep 2026 --> Jan 2026

HER2 expression was associated with epithelial tumor characteristics. The HER2 positive TIME showed reduced immune cell infiltration but also lower expression of inhibitory signals associated with immune exhaustion, questioning the mechanism behind potential clinical benefit of co-administration of anti-HER2 agents and checkpoint inhibitors. As limited response was associated with increased VEGF signalling, studies could investigate potential synergism of targeting VEGF and HER2.

P1, N=114, Active, not recruiting, Mabscale, LLC | Trial completion date: Jun 2024 --> Sep 2024

Hence, the combination of Pyrotinib and Dual HER2 blockade treatment shows promise as a neoadjuvant therapy for locally advanced HER2-positive BC to achieve a pCR in surgery. Nevertheless, this conclusion necessitates additional validation via meticulously designed clinical research investigations encompassing larger patient populations.

P1/2, N=44, Active, not recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=165, Recruiting, MedSIR | Not yet recruiting --> Recruiting

Efficacy, PK, immunogenicity, and safety profiles of ZRC-3277 was found to be similar to those of Perjeta®.

The advent of HER2-targeting monoclonal antibodies such as trastuzumab followed by pertuzumab had improved the prognosis of HER2-positive metastatic BC. In this paper, we summarize the mechanisms of action and resistance of T-DM1 and T-DXd, as well as their clinical efficacy. Additionally, we also discuss potential strategies for addressing resistance to ADC.